Johns Hopkins University, Baltimore, MD
Chen Hu , Mitchell Machtay , James J. Dignam , Rebecca Paulus , Jeffrey D Bradley
Background: OS is the gold standard for LA-NSCLC with CCRT, with complex relationships among RT dosimetry, systemic therapies, cardiopulmonary toxicity, progression (PD) and OS of growing scientific and clinical interest. Methods: RTOG 0617 (NCT00533949) randomized standard (SD, 60 Gy) versus high-dose (HD, 74 Gy) CCRT +/- cetuximab from 11/07-06/11. This analysis includes 469 patients (pts) given ≥50 Gy. A PFS event was defined as the first occurrence of local, regional, distant PD or death w/o documented PD. A CTA-PFS event was the first occurrence of grade 2+ treatment-related cardiac toxicity event or a PFS event. Landmark analyses at 6mo and 12mo were used to minimize the immortal time bias. Cox model with PD or CT/PD as a time-dependent covariate was used to evaluate their predictive roles. Median f/u time for surviving pts was 5.1 years. Results: As reported, pts treated with HD had significantly lower OS rates (HR = 1.28, 95%CI: 1.04-1.58, p = 0.018) and CTA-PFS rates (HR = 1.24, 95%CI: 1.02-1.51, p = 0.035), and marginally lower PFS rates (HR = 1.21, 95%CI: 0.99-1.47, p = 0.06) than pts treated with SD. Median survival time (MST) among pts having PD within 6mo versus not were 13.4mo (95%CI: 10.0-19.0) and 30.7mo (95%CI: 28.0-37.0) (p < 0.001). MST for pts having PD within 12mo versus not were 20.6mo (95%CI: 18.8-25.0) and 60mo (95%CI: 47.6-74.5)(p < 0.001). Results are similar when using CTA-PFS with 6mo or 12mo cutoff (p < 0.001). RT dose was no longer significantly associated with OS (p = 0.08 or p = 0.15) when PD or CT/PD was included in multivariable analysis (p < 0.001), suggesting OS differences in HD/SD may be partially captured by PFS or CTA-PFS. Conclusions: RTOG 0617 survival results suggest that PFS (or CTA-PFS) status at 6mo or 12mo predicts long-term OS, and may potentially be considered as a surrogate endpoint of OS in clinical trials. Pts who were progression-free at 12mo had a MST of 5 years. Further validation on external datasets and in the modern era of immunotherapy are needed.
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